By the development of antisecretory drugs, such as histamine H.sub.2 antagonist and proton pump inhibitor, peptic ulcers, inclusive of a number of ulcers that heretofore required an operation, can now be cured by drug therapy. In view of the fact that most of the ulcers once cured are subject to recurrence and relapse, however, a maintenance therapy over a long period of time is considered to be necessary even after a complete cure, and even during the maintenance therapy, recurrence and relapse are highly frequently observed.
In 1988, Marrshall B. J. et. al. (Lancet ii: 1437-42, 1988) applied eradication of Helicobacter pylori (H. pylori) to H. pylori positive gastric/duodenal ulcer cases, and reported a noticeable decrease in the relapse of duodenal ulcer. Thereafter in 1992, Graham D. Y. et. al. (Ann. Intern. Med. 116:705-708, 1992.) and in 1993, Hentschel E. et. al. (N. Engl. J. Med. 328:308-312, 1993) successively reported that relapse of peptic ulcer decreased significantly in the group subjected to eradication of H. pylori. Given the strong suggestion of the relationship between H. pylori infection, and gastritis and gastric/duodenal ulcer, a bacterial eradication therapy has been tentatively applied to patients with gastric/duodenal ulcer.
In February 1994, the United States National Institutes of Health (NIH) recommended that bacterial eradication therapy should be applied to duodenal ulcer and gastric ulcer, whether on first presentation with illness or recurrence (NIH Consensus Conference: Helicobacter pylori in peptic ulcer disease. JAMA 272:65-69, 1994), and in this year, WHO/IARC reported that H. pylori belonged to group 1 (definite carcinogenic substance) of gastric cancer (WHO International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Schistomsomes, Liver flukes and Helicobacter pylori. Lyon. 61, 177-241, 1994). This report suggests that the target of bacterial eradication therapy for H. pylori is spreading to the treatment and prophylaxis of gastric cancer and gastric malignant lymphoma (Personnet J. et. al., N. Engl. J. Med. 325:1127-1131, 1991, Uemura N. et. al., Gastroenterology 110:A525, 1996).
Considering from these standpoints, bacterial eradication therapy for H. pylori has been actively studied at present. The bacterial eradication therapy for H. pylori include (1) monotherapy represented by amoxicillin, (2) classic triple therapy typically using the combination of a bismuth preparation, metronidazole and tetracycline, (3) dual therapy using a proton pump inhibitor and an antibiotic in combination, and (4) new triple therapy consisting of dual therapy plus an antibiotic, by using proton pump inhibitor and two kinds of antibiotics. However, these therapies are associated with many problems in terms of utility, side effects, emergence of resistant strains and compliance, and there has not been established a safe and reliable bacterial eradication therapy. In addition, since many are combined therapies, the dose and administration period of the drugs have not been necessarily consistent. This explains difference in bacterial eradication rates that varied depending on the organizations that enforced the investigation.
Taking note of the superior antibacterial property of new quinolone compounds, there have been recently reported extended application as an anti-H. pylori drug of available levofloxacin, and antibacterial activity of trovafloxacin (34th ICAAC (Orlando, USA): F-24, 1994) and DU-6859a (33rd ICAAC (New Orleans, USA): Abstr. 1188, 1993) against H. pylori.
In these studies in vitro antibacterial activity against H. pylori and in vivo bacterial eradication effect do not always correlate, and they have not amounted to the establishment of a safe and reliable bacterial eradication treatment.
In view of the above, there is a demand for a pharmaceutical agent having superior anti-H. pylori activity in vitro and superior bacterial eradication of H. pylori in vivo, which is useful for the eradication of H. pylori from the patients with gastritis/peptic ulcer, for the treatment of gastritis/peptic ulcer or for the prevention of recurrence/relapse thereof.